Stent with protruding branch portion for bifurcated vessels

ABSTRACT

The present invention is directed to a stent for use in a bifurcated body lumen having a main branch and a side branch. The stent comprises a radially expandable generally tubular stent body having proximal and distal opposing ends with a body wall having a surface extending therebetween. The surface has a geometrical configuration defining a first pattern, and the first pattern has first pattern struts and connectors arranged in a predetermined configuration. The stent also comprises a branch portion comprised of a second pattern, wherein the branch portion is at least partially detachable from the stent body.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims the benefit of U.S. ProvisionalApplication No. 60/404,756, filed Aug. 21, 2002, U.S. ProvisionalApplication No. 60/487,226, filed Jul. 16, 2003, and U.S. ProvisionalApplication No. 60/488,006, filed Jul. 18, 2003, the entire contents ofwhich are incorporated herein by reference.

The present application is a continuation-in-part of now abandoned U.S.patent application Ser. No. 09/668,687, filed Sep. 22, 2000, which was acontinuation-in-part of U.S. patent application Ser. No. 09/326,445,filed Jun. 4, 1999, which issued as U.S. Pat. No. 6,325,826. The presentapplication is also a continuation-in-part of U.S. patent applicationSer. No. 10/440,401, filed May 19, 2003 which is a continuation of U.S.patent application Ser. No. 09/750,372, filed Dec. 27, 2000, whichissued as U.S. Pat. No. 6,599,316. The present application is also acontinuation-in-part of U.S. patent application Ser. No. 09/963,114,filed Sep. 24, 2001, which issue as U.S. Pat. No. 6,706,062, and whichis a continuation of U.S. patent application Ser. No. 09/326,445, filedJun. 4, 1999, now U.S. Pat. No. 6,325,826. U.S. patent application Ser.No. 09/326,445 is continuation-in-part of PCT Application No.US99/00835, filed Jan. 13, 1999, which claims the benefit of U.S. patentapplication Ser. No. 09/007,265, filed Jan. 14, 1998, which issued asU.S. Pat. No. 6,210,429, which is a continuation-in-part of nowabandoned of U.S. patent application Ser. No. 08/744,002, filed Nov. 4,1996. The entire contents of all of the above references areincorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to the field of medical stents and, moreparticularly, to a stent for the treatment of lesions and other problemsin or near a vessel bifurcation.

BACKGROUND OF THE INVENTION

A stent is an endoprosthesis scaffold or other device that typically isintraluminally placed or implanted within a vein, artery, or othertubular body organ for treating an occlusion, stenosis, aneurysm,collapse, dissection, or weakened, diseased, or abnormally dilatedvessel or vessel wall, by expanding the vessel or by reinforcing thevessel wall. In particular, stents are quite commonly implanted into thecoronary, cardiac, pulmonary, neurovascular, peripheral vascular, renal,gastrointenstinal and reproductive systems, and have been successfullyimplanted in the urinary tract, the bile duct, the esophagus, thetracheo-bronchial tree and the brain, to reinforce these body organs.Two important current widespread applications for stents are forimproving angioplasty results by preventing elastic recoil andremodeling of the vessel wall and for treating dissections in bloodvessel walls caused by balloon angioplasty of coronary arteries, as wellas peripheral arteries, by pressing together the intimal flaps in thelumen at the site of the dissection. Conventional stents have been usedfor treating more complex vascular problems, such as lesions at or nearbifurcation points in the vascular system, where a secondary arterybranches out of a larger, main artery, with limited success rates.

Conventional stent technology is relatively well developed. Conventionalstent designs typically feature a straight tubular, single type cellularstructure, configuration, or pattern that is repetitive throughtranslation along the longitudinal axis. In many stent designs, therepeating structure, configuration, or pattern has strut and connectingmembers that impede blood flow at bifurcations. Furthermore, theconfiguration of struts and connecting members may obstruct the use ofpost-operative devices to treat a branch vessel in the region of avessel bifurcation. For example, deployment of a first stent in the mainlumen may prevent a physician from inserting a branch stent through theostium of a branch vessel of a vessel bifurcation in cases wheretreatment of the main vessel is suboptimal because of displaced diseasedtissue (for example, due to plaque shifting or “snow plowing”),occlusion, vessel spasm, dissection with or without intimal flaps,thrombosis, embolism, and/or other vascular diseases. As a result, thephysician may choose either to insert a stent into the branch in casesin which such additional treatment may otherwise be unnecessary, oralternatively the physician may elect not to treat, or to “sacrifice”,such side lumen. Accordingly, the use of regular stents to treatdiseased vessels at or near a vessel bifurcation may create a risk ofcompromising the benefit of stent usage to the patient after the initialprocedure and in future procedures on the main vessel, branch vessels,and/or the bifurcation point.

A regular stent is designed in view of conflicting considerations ofcoverage versus access. For example, to promote coverage, the cellstructure size of the stent may be minimized for optimally supporting avessel wall, thereby preventing or reducing tissue prolapse. To promoteaccess, the cell size may be maximized for providing accessibility ofblood flow and of a potentially future implanted branch stent to branchvessels, thereby preventing “stent jailing”, and minimizing the amountof implanted material. Regular stent design has typically compromisedone consideration for the other in an attempt to address both. Problemsthe present inventors observed involving side branch jailing, fear ofplaque shifting, total occlusion, and difficulty of the procedure arecontinuing to drive the present inventors' into the development ofnovel, non-conventional or special stents, which are easier, safer, andmore reliable to use for treating the above-indicated variety ofvascular disorders.

Although conventional stents are routinely used in clinical procedures,clinical data shows that these stents are not capable of completelypreventing in-stent restenosis (ISR) or restenosis caused by intimalhyperplasia. In-stent restenosis is the reoccurrence of the narrowing orblockage of an artery in the area covered by the stent following stentimplantation. Patients treated with coronary stents can suffer fromin-stent restenosis.

Many pharmacological attempts have been made to reduce the amount ofrestenosis caused by intimal hyperplasia. Many of these attempts havedealt with the systemic delivery of drugs via oral or intravascularintroduction. However, success with the systemic approach has beenlimited.

Systemic delivery of drugs is inherently limited since it is difficultto achieve constant drug delivery to the inflicted region and sincesystemically administered drugs often cycle through concentration peaksand valleys, resulting in time periods of toxicity and ineffectiveness.Therefore, to be effective, anti-restenosis drugs should be delivered ina localized manner.

One approach for localized drug delivery utilizes stents as deliveryvehicles. For example, stents seeded with transfected endothelial cellsexpressing bacterial beta-galactosidase or human tissue-type plasminogenactivator were utilized as therapeutic protein delivery vehicles. See,e.g., Dichek, D. A. et al., “Seeding of Intravascular Stents WithGenetically Engineered Endothelial Cells”, Circulation, 80: 1347–1353(1989).

U.S. Pat. No. 5,679,400, International Patent Application WO 91/12779,entitled “Intraluminal Drug Eluting Prosthesis,” and InternationalPatent Application WO 90/13332, entitled “Stent With Sustained DrugDelivery” disclose stent devices capable of delivering antiplateletagents, anticoagulant agents, antimigratory agents, antimetabolicagents, and other anti-restenosis drugs.

U.S. Pat. Nos. 6,273,913, 6,383,215, 6,258,121, 6,231,600, 5,837,008,5,824,048, 5,679,400 and 5,609,629 teach stents coated with variouspharmaceutical agents such as Rapamycin, 17-beta-estradiol, Taxol andDexamethasone.

Although prior art references disclose numerous stents configurationscoated with one or more distinct anti-restenosis agents, they do notdisclose the inventive stent design of the present application. Thereis, therefore, a need for a stent design that can effectively provideostial branch support in a vessel bifurcation and effectively act as adelivery vehicle for drugs useful in preventing restenosis. This isparticularly true in complicated cases, such as lesions located at abifurcation.

SUMMARY OF THE INVENTION

The present invention is directed to a stent for use in a bifurcatedbody lumen having a main branch and a side branch. The stent comprises aradially expandable generally tubular stent body having proximal anddistal opposing ends with a body wall having a surface extendingtherebetween. The surface has a geometrical configuration defining afirst pattern, and the first pattern has first pattern struts andconnectors arranged in a predetermined configuration. The stent alsocomprises a branch portion comprised of a second pattern, wherein thebranch portion is at least partially detachable from the stent body.

In one embodiment, the second pattern is configured according to thefirst pattern having at least one absent connector, and in anotherembodiment, the second pattern has a plurality of absent connectors. Thesecond pattern may have second pattern struts, and the second patternstruts can be more densely packed than the first pattern struts.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawings. With specific reference now tothe drawings in detail, it is stressed that the particulars shown are byway of example and for purposes of illustrative discussion of thepreferred embodiments of the present invention only, and are presentedto provide what is believed to be the most useful and readily understooddescription of the principles and conceptual aspects of the invention.In this regard, no attempt is made to show structural details of theinvention in more detail than is necessary for a fundamentalunderstanding of the invention, the description taken with the drawingsmaking apparent to those skilled in the art how the invention may beembodied in practice.

In the drawings:

FIG. 1 is an illustration of a blood vessel bifurcation having anobstruction;

FIGS. 2–4 are illustrations of prior art stents implemented at a bloodvessel bifurcation;

FIG. 5 is a flat view of an embodiment of an unexpanded stent inaccordance with the present invention;

FIG. 6 is an enlarged view of a portion of the unexpanded stent shown inFIG. 5;

FIG. 7 is a perspective view of the expandable branch portion of thestent of FIG. 5 in the expanded configuration;

FIG. 8 is an enlarged view of a portion of another embodiment of a stentaccording to the present invention;

FIG. 9 is an enlarged view of a portion of an alternative embodiment ofa stent according to the present invention;

FIG. 10 is a perspective view of the expandable branch portion of thestent of FIG. 9 in the expanded configuration;

FIG. 11 is a schematic view of the stent of FIG. 5 in the expanded stateimplemented at a blood vessel bifurcation;

FIG. 12 is a schematic view of the stent of FIG. 9 in the expanded stateimplemented at a blood vessel bifurcation;

FIG. 13 is an enlarged view of a portion of another embodiment of astent according to the present invention;

FIG. 14 is a flat view of another embodiment of an unexpanded stent inaccordance with the present invention;

FIG. 15 is an enlarged view of a portion of the unexpanded stent shownin FIG. 14;

FIG. 16 is a view of a portion of another embodiment of a stentaccording to the present invention;

FIG. 17 is a flat view of another embodiment of an unexpanded stent inaccordance with the present invention;

FIG. 18 is a perspective view of the expandable branch portion of thestent of FIG. 17 in the expanded configuration;

FIG. 19 is a flat view of another embodiment of an unexpanded stent inaccordance with the present invention;

FIG. 20 is an enlarged view of a portion of the stent of FIG. 19;

FIG. 21 is a view of the expandable branch portion of the stent of FIG.19 in the expanded configuration;

FIG. 22 is a flat view of another embodiment of an unexpanded stent inaccordance with the present invention;

FIG. 23 is a flat view of another embodiment of an unexpanded stent inaccordance with the present invention;

FIG. 24 is a view of an expandable branch portion of the stent of FIG.23 in the expanded condition;

FIGS. 25–28 are illustrations of the steps for a method of inserting astent of the present invention, according to one embodiment.

FIGS. 29–31 are illustrations of the steps for another method ofinserting a stent of the present invention.

FIG. 32 is a view of a herniated balloon for use with the method ofFIGS. 29–31; and

FIG. 33 is a view of another stent delivery system for inserting a stentin accordance with another method of the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention relates to stents for placement at vesselbifurcations and are generally configured to at least partially cover aportion of a branch vessel as well as a main vessel. Referring to FIG.1, an exemplary blood vessel bifurcation 1 is shown, having a mainvessel 2 extending along a main vessel axis 3 and a branch vessel 4extending along a branch vessel axis 5. Main vessel 2 and branch vessel4 are disposed at an angle 11 of less than 90 degrees. An obstruction 6is located within bifurcation 1, spanning or at least partiallyobstructing main vessel 2 and a proximal portion branch vessel 4.

Prior attempts at relieving main vessel 2 and branch vessel 4 fromobstruction 6, such as the one depicted in FIG. 1, have beenproblematic. Referring to FIGS. 2–4, examples of prior methods andstructures for stenting an obstructed bifurcation are shown. As shown inFIG. 2, a first stent 8 is introduced into main vessel 2 and an accesshole or side opening in the wall of stent 8 is usually created with aballoon to provide access to branch vessel 4 and unobstructed blood flowthereto. Typically, the access hole is created by deforming the strutsand connectors of the main stent pattern, which may also deform the areaof the stent surrounding the created opening and lead to undesirableresults. Also, if stent 8 is used alone, at least a portion ofobstruction 6 located within branch vessel 4 is left without stentcoverage. Referring to FIGS. 3 and 4, one prior solution has been tointroduce a second stent 10 into branch vessel 4, for example via asecond catheter inserted through a side opening of first stent 8. As canbe seen in FIGS. 3 and 4, such a configuration may introduce additionalproblems. For example, as shown in FIG. 3, second stent 10 may notprovide full coverage of the portion of obstruction 6 in branch vessel 4due to the angle 11 of the side branch vessel 4 with respect to mainvessel 2 and the fact that the ends of the stent typically define aright angle to the longitudinal axis of the lumen. Alternatively, secondstent 10 may extend beyond the bifurcation into main vessel 2, as shownin FIG. 4, and cause potential obstruction of blood flow in main vessel2 and/or cause problems at the overlapping portions of stents 8 and 10.

Referring now to FIGS. 5–7, a stent 12 according to one embodiment ofthe present invention comprises stent body or wall 14 extending along alongitudinal axis 16 from a proximal end 20 to a distal end 22 anddefining a lumen 18 therein. Stent 12 may have a three-dimensionalgeometrical configuration having variable dimensions (length, width,height, depth, thickness, etc.). In a preferred embodiment, stent body14 is a generally tubular structure. As defined herein, “tubular” caninclude an elongate structure that has varied cross-sections and doesnot require that the cross-section be circular. For example, thecross-section of stent wall 14 may be generally oval. In an alternateembodiment, stent body 14 is generally cylindrical. Also, the stent body14 may have varied cross-sectional shapes along the longitudinal axis 16of the stent. For example, the circumferences in the proximal and distalparts of the stent may be different. This may occur, for example, ifduring stent delivery the delivery system causes the stent to distend.Lumen 18 represents the inner volumetric space bounded by stent body 14.In a preferred embodiment, stent 12 is radially expandable from anunexpanded state to an expanded state to allow the stent to expandradially and support the main vessel. In the unexpanded state, stentbody 14 defines a lumen 18 having a first volume, and in the expandedstate, stent body 14 defines a lumen 18 having a second volume largerthan the first volume.

FIG. 5 shows stent 12 in an unexpanded state in a flattened elevationalview. As shown in FIG. 5, stent body 14 has a generally cellularconfiguration and comprises a generally repeatable series of struts 24and connectors 26 configured in a predetermined general, overall, ormain pattern along the length of stent 12. Struts 24 comprise a pair oflongitudinal strut portions 25 joined by a curved portion 27 at theproximal ends. Struts 24 are interconnected by curved portion 29 at thedistal ends and formed into rings 28 that extend about the circumferenceof stent 12. A series of the circumferential rings 28 are spaced apartfrom one another longitudinally along the entire length of stent 12, andconnectors 26 connect rings 28 to each other longitudinally. Connectors26 extend generally longitudinally between adjacent circumferentialrings 28 and connect to the respective curved portions 27, 29 oflongitudinally adjacent struts 24 of adjacent rings 28. In a preferredembodiment, connectors 26 are generally S-shaped or zigzag-shaped,although other patterns may also be used. Details of patterns that maybe used for stent 12 are described more fully in co-pending PCTapplication IL02/00840, filed Oct. 20, 2002, incorporated herein byreference in its entirety. Furthermore, many other strut and connectorpatterns may be used, and the present pattern is shown for illustrationpurposes only.

Stent 12 further includes a branch portion 30 located at some pointalong the length of stent 12. Branch portion 30 comprises a section orportion of stent wall 14 that is configured to extend into a branchvessel in a vessel bifurcation. In general, branch portion 30 isconfigured to be movable from an unextended position to an extendedposition. In the unextended position, branch portion 30 is disposed inthe volume defined by the unexpanded stent 12, that is, the branchportion 30 does not protrude radially from stent wall 14. In theextended position, the branch portion 30 extends outwardly from stentwall 14 and branch portion 30 is extended into the branch vessel. Asbest seen in FIG. 6, branch portion 30 comprises a stent wall section ofstent body 14 that is initially flush, coplanar, or cocylindrical withthe remainder of stent body 14 and may extend outwardly with respect tothe remainder of stent body 14. In this regard, branch portion 30 isgenerally adjacent an opening, slit, space, void, or other incongruityin the overall or main pattern of stent body 14. This configurationallows for access into a branch vessel, and at the same time allows forcircumferential alignment of the stent within the vessel prior todeployment. In other embodiments, multiple branch portions can beincorporated into the stent to permit multiple access to one or morevessels. In a preferred embodiment, branch portion 30 may be positionedin the midsection of stent 12. In alternate embodiments, branch portion30 may be positioned anywhere along the length of stent 12.

As best seen in FIG. 6, in a first embodiment, branch portion 30comprises a portion of branch ring 32 and is positioned adjacent andproximal to an opening 34. Upon extension of branch portion 30, theportion of branch ring 32 adjacent opening 34 extends into the branchvessel, whereas the circumferential ring 28 adjacent branch ring 32 doesnot extend into the branch vessel. Opening 34 is formed by an absence ofat least one connector 26 adjoining branch ring 32 with a branchopposing ring 33. In some embodiments, four adjacent connectors areabsent; however, in alternate embodiments any number of connectors maybe absent to create opening 34. In this embodiment, branch ring 32 issubstantially similar geometrically to circumferential rings 28 andcomprises branch ring struts 36 substantially similar to struts 24;however, a plurality of adjacent struts are free from connectors 26adjacent opening 34. In this regard, branch ring 32 is at leastpartially detachable from stent body 14 to facilitate at least a portionof branch ring 32 to extend outwardly with respect to stent body 14. Insome embodiments, the geometry of branch ring 32 may vary with respectto circumferential rings 28, and branch ring struts 36 may havedifferent configurations than struts 24.

When stent 12 is expanded, as shown in FIG. 7, branch portion 30 isextended into the branch vessel, causing a portion of branch ring 32 toat least partially cover the inner surface of the branch vessel 4. Thus,in a preferred embodiment, the stent coverage in the branch vesselincludes at least partial coverage of the proximal side of the innerbranch vessel wall.

Various alternative embodiments provide varying geometries of branchportion 30. For example, branch ring 32 may vary with respect tocircumferential rings 28, and branch ring struts 36 may have differentconfigurations than struts 24. In one alternate embodiment, branch ringstruts 36 are longer than struts 24. In another embodiment, branch ringstruts 36 are more closely packed circumferentially, resulting in agreater number of branch ring struts 36 per area within branch ring 32as compared to circumferential rings 28. In another embodiment, branchring struts 36 may be thinner than struts 24. In yet another embodiment,branch ring struts 36 may be made of a different material than struts24.

Referring to FIG. 8, another alternate embodiment of stent 19 is shownwherein a branch portion 30 comprises a branch ring 32 having branchring struts 36 that are longer than struts 24 and a greater number ofbranch ring struts 36 provided as compared to the number of struts 24 incircumferential rings 28, resulting in a more closely packed branch ring32. Furthermore, the number of branch ring connectors 38 on both sidesof branch ring 32 is lower per branch strut 36 than the number ofconnectors 26 per strut 24. Opening 34 is adjacent branch ring 32 on adistal side thereof, and the distal ends 46 of at least one, andpreferably a plurality, of branch ring struts 40, 42, 44 are free fromconnectors and detachable from stent body 14. In this embodiment, twobranch ring struts 48 and 50 positioned laterally adjacent struts 40,42, and 44 have proximal ends 52 free from connectors. In this regard,free proximal ends 52 provide less resistance to movement of branch ring32 during outward expansion with respect to stent body 14. This sameprocedure can be used to provide one, two, three or more proximal endsin the ring free of connectors. Additionally, the shape andconfiguration of branch ring connectors 38 is different than those ofconnectors 26. For example branch ring connectors along the proximalside of branch ring 32 are longer than connectors 26 to facilitategreater expansion of branch portion 30 into a vessel side branch. Also,branch ring connectors along the distal side of branch ring 32 areshaped and oriented differently than connectors 26 to facilitate greaterexpansion of branch portion 30 into the branch vessel. In alternateembodiments, branch ring connectors 38 may also differ among themselves.Also, the longer branch ring struts 36 are generally more flexible thancomparable shorter struts because the added length permits moredeflection. Also, the added length permits greater coverage vessel wallcoverage due to deeper penetration into the branch vessel duringextension. In alternate embodiments, different geometries andorientations of branch ring connectors 38 may be used.

Referring to FIG. 9, another alternate embodiment of stent 29 is shownhaving a branch portion 30 similar to that of the embodiment of FIG. 8,except branch ring struts 40, 42, and 44 are longer than the otherbranch ring struts 36, and the distal ends thereof define an arcuateprofile to the proximal side of opening 34. Also, central strut 42 islonger than struts 40, 44 adjacent to strut 42. In this regard, whenbranch portion 30 is extended, struts 40, 42, and 44 extend further intothe branch vessel and provide more coverage of the vessel wall than theembodiment depicted in FIG. 8. In this regard, this embodiment may morereadily cover an obstruction in a bifurcation vessel such as the onedepicted in FIG. 1 and, therefore, may provide better blood flow to abranch vessel. Furthermore, as described in more detail below, thisembodiment facilitates the use of a second stent in the branch vessel.

Referring to FIG. 10, stent 29 of FIG. 9 is shown in an expanded statewith branch portion 30 extended into the branch vessel, causing branchring 32 to at least partially cover the inner surface of the branchvessel on the proximal side. The distal end of strut 42 of branch ring32 extends further into the branch vessel than the distal ends of struts40, 44 because strut 42 is longer in this embodiment than adjacentstruts 40, 44. In this regard, a generally tapered, straight or linearprofile along the distal perimeter of branch portion 30 is created whenbranch portion 30 is expanded into the branch vessel.

Referring to FIGS. 11 and 12, schematic views are shown of stents 12, 29of FIGS. 5 and 9, respectively, in the expanded state as implemented ata blood vessel bifurcation. As shown in FIG. 11, stent 19 of theembodiment of FIG. 8 has a generally curved or radial profile along thedistal perimeter 45 of branch portion 30 as it extends into branchvessel 4. The generally curved or radial profile is due to theparticular geometry of branch portion 30 of stent 19 of the embodimentof FIG. 8. In particular, because all of the branch ring struts 36 ofbranch ring 32 are of equal length in this embodiment, the distal endsof struts 36 radially expand equidistantly into branch vessel 4, therebycreating a generally curved or radial profile along the distal perimeter45 of branch portion 30. Referring to FIG. 12, stent 29 of theembodiment of FIG. 9 has a generally tapered, straight or linear profilealong the distal perimeter 47 of the branch portion 30 of the stent asit extends into branch vessel 4. The generally straight or linearprofile in FIG. 12 is a result of the particular geometry of branchportion 30 of stent 29 of the embodiment of FIG. 9. In particular,because central strut 42 of branch ring 32 is longer in this embodimentthan struts 40, 44 adjacent to strut 42, the distal end of strut 42extends further into branch vessel 4 than the distal ends of struts 40,44, as best seen in FIG. 10, thus creating a generally tapered, straightor linear profile along the distal perimeter of branch portion 30. In apreferred embodiment, the linear profile is at a right angle withrespect to the axis of branch vessel 4. In alternative embodiments,however, the linear profile may be at any angle with respect to the axisof branch vessel 4. One advantageous feature of the linear profile alongthe distal perimeter of branch portion 30 shown in FIG. 12 is that if asecond stent 51 were to be used in branch vessel 4, the linear profilefacilitates better alignment with the second stent and permits coverageof a larger surface area of the branch vessel wall. For example, if asecond stent 51 were to be used in combination with stent 12 of FIG. 11,gaps may exist between the two stents at the interface between theradial distal perimeter 45 and an abutting straight or linear edge of asecond stent, whereas a close abutting interface may be achieved withstent 29 of FIG. 12.

Referring to FIG. 13, another embodiment of stent 39 is shown having analternative embodiment of a branch portion 30 similar to that of theembodiment of FIG. 9, except lateral branch ring struts 48 and 50 arelonger than the other branch ring struts 36, and the proximal ends 52 ofbranch ring struts 48, 50 extend proximally beyond the other branch ringstruts into a space between the branch ring 32 and the adjacentcircumferential ring 28. Branch ring struts 48, 50 have proximal ends 52free from connectors and provide less resistance to movement of branchring 32 during outward expansion with respect to stent body 14. In thisregard, the longer lateral branch ring struts 48, 50 function similar toa hinge and further facilitate extension of branch ring portion 30outwardly, which may accommodate a branch vessel disposed at a greaterangle 11 (FIG. 1) as compared to stent 29 of the embodiment of FIG. 9.Again, since struts 40, 42, and 44 are longer than branch ring struts36, they are more flexible and provide more coverage of a vessel wallthan the embodiment depicted in FIG. 8.

Referring now to FIGS. 14 and 15, another embodiment of stein 49 isshown having a stent body 14 that has a Longitudinal section 53 that hasa different pattern than main pattern 54. Longitudinal section 53comprises a generally repeatable series of struts 56 and connectors 58that are smaller in dimension than struts 24 and connectors 26, but areformed into a similar geometrical pattern as main pattern 54. In thisregard, the struts 56 are more numerous per area within rings 28, andrings 28 are more numerous per area in section 53 because the length ofstruts 56 is shorter than the length of struts 24 and the length ofconnectors 58 is shorter than the length of connectors 26. In apreferred embodiment, the same number of connectors 58 extend betweenadjacent rings 28; however, because the struts are more numerous inlongitudinal section 53, connectors 58 extend longitudinally betweenevery other strut of adjacent rings 28. As shown in FIG. 15, stent 49Thither includes a branch portion 30 positioned within section 53.Branch portion 30 comprises a branch ring 32 adjacent an opening 34.Opening 34 is formed by an absence of at least one connector 58adjoining branch ring 32 with branch opposing ring 33. In a preferredembodiment, two adjacent connectors are absent; however, in alternateembodiments any number of connectors maybe absent to create opening 34.In this embodiment, branch ring 32 is substantially similargeometrically to circumferential rings 28 and comprises branch ringstruts 36 substantially similar to struts 56; however, a plurality ofadjacent struts are free from a connectors 58 adjacent opening 34 andbranch ring 32 is at least partially detachable from stent body 14 atopening 34 to facilitate at least a portion of branch ring 32 to extendoutwardly with respect to stent body 14. The generally smaller strutsand connectors of longitudinal section 53 provide for freer movement ofthe strut and connector material and facilitate conformance to a vesselwall. The smaller struts and connectors also provide for a relativelymore dense surface area coverage of the branch vessel wall, which may beadvantageous in achieving a more uniform coverage around the ostium. Inparticular, this embodiment may provide particularly advantageouscoverage of a geometrically complex obstruction in a bifurcation vesselsince the relatively small pattern may flex or contour around theobstruction and provide coverage therefor. Also, this embodiment isadvantageous for relatively small obstructions as the smaller patternmay cover more surface area of obstruction.

Referring to FIG. 16, another embodiment of stent 59 is shown andincludes an alternate branch portion 30 comprising a portion of threeadjacent branch ring sections 60, 62, 64 connected and extendingcircumferentially from two adjacent circumferential rings 28. Branchring sections 60, 62, 64 each includes a plurality of branch struts 66and are connected in the longitudinal direction by branch connectors 68.Struts 66 are shorter longitudinally than struts 24 of rings 28 andconnectors 68 are smaller than connectors 26. The distal ring 60 isadjacent opening 34 and the distal ends of struts 66 of ring 60 aredetachable from stent body 14 at opening 34 to permit extension of atleast a portion of branch ring sections 60, 62, 64 to expand outwardlywith respect to stent body 14. In this embodiment, the three branch ringsections 60, 62, 64 may extend outwardly in a more radial fashion andthis branch portion 30 may be particularly advantageous for adapting orconforming to the shape of the proximal side of the ostium. Furthermore,the branch portion of this embodiment may more readily extend or flexaround an obstruction in a bifurcation vessel such as the one depictedin FIG. 1 while providing branch wall coverage and better blood flow tothe branch vessel.

Referring to FIGS. 17 and 18, an alternate embodiment of stent 69 isshown and includes an alternate branch portion 30. In this particularembodiment, branch portion 30 comprises support struts 70 and anexpandable ring 72. Branch portion 30 defines at least one side opening74. In one embodiment, the dimensions of the cell defining side opening74 are such that the side opening 74 (prior to expansion of the stent)is larger than other openings in stent body 14. The presence of sideopening 74 is generally configured to accommodate a side sheaththerethrough and allow a physician to access a branch vessel during orafter a procedure. In a particular embodiment, as shown in FIG. 17, sideopening 74 is surrounded by expandable ring 72 of continuous material.In alternative embodiments, expandable ring 72 comprises unattachedportions, or one portion that only partially covers side opening 74. Aseries of support struts 70 connect expandable ring 72 with struts 24and connectors 26. Support struts 70 preferably comprise patterns in afolded or wrap-around configuration that at least partially straightenout during expansion, allowing expandable ring 72 to protrude into thebranch vessel.

In this embodiment, when stent 69 is expanded, as shown in FIG. 18,branch portion 30 is extended into the branch vessel, causing expandablering 72 to at least partially cover the inner surface of the branchvessel. Thus, in a preferred embodiment, the stent coverage in a portionthe branch vessel includes the full circumference of the inner branchvessel wall. In alternative embodiments, partial coverage or severalsections of coverage are present.

Referring to FIGS. 19–21, another embodiment of a stent 79 is shownhaving a main stent body 14 and another embodiment of a branch portion30. FIGS. 19 and 20 show stent 79 in the unexpanded condition wherebranch portion 30 has not been deployed. FIG. 21 shows the stent 79 inthe expanded configuration where the branch portion 30 has beenexpanded. As shown, main stent body 14 includes a main stent patternhaving a generally repeatable ring 28 and connector 26 pattern. Branchportion 30 and the surrounding midsection 80 interrupt the repeatablering 28 and connector 26 pattern of stent 79. In this embodiment, branchportion 30 is configured to be both radially expandable andlongitudinally extendable into the branch vessel and relative to itslongitudinal axis 83 so that, in a preferred embodiment, the branchportion 30 contacts the entire periphery or circumference of the innerwall of the branch vessel in the expanded configuration. In this regard,branch portion 30 preferably provides 360° coverage of the wall of thebranch vessel. That is, branch portion 30 can be extended outward withrespect to longitudinal axis 81 of stent 79, and can also be expandedradially about axis 83 so as to contact the vessel (thereby allowing itto be adjustable with respect to vessel size).

Referring to FIG. 20, an enlarged view of section 80 of stent 79 isshown. In a preferred embodiment, a structural support member 84 may beprovided as a transition between the main stent body 14 and branchportion 30. In one aspect of a preferred embodiment, structural supportmember 84 may be elliptical to accommodate branch vessels extending atan angle to the main vessel. In alternate embodiment, other shapes ofsupport member 84 can be used to accommodate the vasculature. Thestructural support member 84 may include a continuous ring. In thisembodiment, structural support member 84 is a full, non-expandable ringand it does not expand radially beyond a particular circumference.

As shown in FIGS. 19 and 20, two concentric rings, inner ring 86 andouter ring 88, are positioned within structural support member 84 andsurround a generally circular central branch opening 34 to provideaccess to the side branch vessel when stent 79 is in the unexpandedcondition. Rings 86 and 88 are interconnected by a plurality of innerconnectors 90. Outer ring 88 is connected to structural support member84 by a plurality of outer connectors 92. Rings 86 and 88 are generallycurvilinear members. For example, rings 86, 88 can be defined byundulation petals, prongs, or peaks 94. In a preferred embodiment, eachring 86, 88 have the same number of undulation peaks 94, but the innerring may be more closely or tightly arranged, as shown. In anotherpreferred embodiment, each ring 86, 88 has eight pedals or undulationpeaks 94, although in alternate embodiments each ring can have anynumber of undulation peaks, and the number of peaks need not be equalfor each ring. The undulation peaks 94 generally include a pair of strutportions 96 interconnected by curved portions 98, and the strut portionsthemselves are connected to adjacent strut portions by another curvedportion. In a preferred embodiment, eight outer connectors 92 extendbetween structural support member 84 and outer ring 88, and each outerconnector 92 is attached at one end to approximately the middle of astrut portion 96 of outer ring 88 and the structural support member 84at the other end. As shown, outer connectors 92 may also have anundulated shape, although in alternate embodiments outer connectors 92may have differing shapes. In another aspect of the preferredembodiment, outer connectors 92 may be evenly or symmetrically spacedabout the structural support member 84. The inner ring 86 is attached tothe outer ring 88 by a plurality of inner connectors 90 and, in apreferred embodiment, eight inner connectors 90 connect the rings. Innerconnectors 90 extend from curved portion 98 of outer ring 88 to curvedportion of inner ring 86. As shown in FIG. 20, in a preferredembodiment, inner connectors 90 have a simple curved shape. Otherquantities, configurations, sizes and arrangements of connectors, ringsand spacing can be used depending upon the desired results. Varying theconnectors can provide for different amounts of flexibility andcoverage. The type of configuration of rings and connectors shownaddresses the need for radial and longitudinal expansion of branchportion 30, as well as branch vessel coverage. Other configurations andarrangements for the branch portion can be used in accordance with theinvention.

Referring again to FIGS. 19 and 20, the stent pattern surrounding branchportion 30 may be modified with a different pattern to accommodatebranch portion 30, as can all of the aforementioned embodiments. Inparticular, the rings 28 in the midsection 80 may be configured anddimensioned to be denser to provide sufficient coverage and flexibilityto compensate for the area occupied by branch portion 30.

Referring now to FIG. 21, stent 79 is shown in the expandedconfiguration, with branch portion 30 deployed. Upon expansion of branchportion 30, the inner and outer rings 86, 88 shift about thelongitudinal branch axis 83 and expand laterally away from the mainstent body 14 and into the branch vessel to form a branch coverageportion. Upon expansion, the outer connectors 92 can move outwardly andthe inner connectors 90 can straighten to a position substantiallyparallel to longitudinal branch axis 83. In a preferred embodiment, theexpanded rings 86, 88 have substantially the same expanded diameter,although in alternate embodiments rings 86, 88 could also have differentdiameters to accommodate a tapered vessel, if, for example a taperedballoon is used. The branch portion 30 can be extended at differentangles to the longitudinal axis 81 of the stent depending upon thegeometry of the branch vessel being treated. In this embodiment, thebranch portion 30 may preferably extend into the branch vessel about1.5–3 mm.

Referring now to FIG. 22, another embodiment of a stent 89 is shownhaving a main stent body 14 and another embodiment of a branch portion30. Stent 89 is substantially similar to stent 79, except stent 89 has adiscontinuous support member 104 surrounding a two concentric ring 86,88 structure. Support member 104 has a generally elliptical shape andincludes a plurality of discontinuities 106 along the perimeter. Theconfiguration of the discontinuous support member facilitates additionalflexibility of the branch portion during expansion and generallyprovides for accommodating a greater range of branch vessel geometries.In one aspect of a preferred embodiment, structural support member 104may be elliptical to accommodate branch vessels extending at an angle tothe main vessel.

Referring to FIGS. 23 and 24, another embodiment of a stent 99 is shownin the unexpanded and expanded states, respectively. Stent 99 comprisesa main stent body 14 and another embodiment of a branch portion 30.Stent 99 is substantially similar to stent 79, except stent 99 has abranch portion 30 including a support member 108 surrounding threeconcentric rings: a first ring 110, a second ring 112, and a third ring114 instead of two. First ring 114 is connected to the support member108 by an outer or first connector 92. The first ring 114 defines acomplete circuit which extends without interruption from the first sideor clockwise side 92′ of the first connector to the second side orcounterclockwise side 92″ of the first connector 92. The second ring 112is connected to the first ring 114 by an inner or second connector 90.As with the first ring 114, the second ring 112 defines a completecircuit which extends without interruption from the first side orclockwise side 90′ of the second connector 90 to the second side orcounterclockwise side 90″ of the second connector 90. As can be seen inFIG. 24, when stent 99is expanded the three concentric ring structure ofthis embodiment facilitates additional branch wall support because agenerally more dense pattern is created in branch portion 30 wit theaddition of another concentric ring.

In all of the above embodiments, the branch portion 30 protrudes intothe branch vessel when the stent is fully expanded. The branch portionupon expansion can extend into the branch vessel in different lengthsdepending upon the application. The amount of extension may vary in arange between about 0.1–10.0 mm. In one preferred embodiment, the lengthof extension is 1–3 mm. In another preferred embodiment, the length ofextension is approximately 2 mm. In alternative embodiments, the amountof extension into the branch vessel may be variable for differentcircumferential segments of branch portion 30. As shown in each of theembodiments, the branch portion is approximately 2.5 mm in width andabout 2.5–3.0 mm in length. However, the branch portion can bedimensioned to accommodate varying size branch vessels. The branchportion can be formed of any tubular shape to accommodate the branchvessel, including, oval or circular, for example.

In general, a wide variety of delivery systems and deployment methodsmay be used with the aforementioned stent embodiments. For example, acatheter system may be used for insertion and the stent may be balloonexpandable or self-expandable, or the stent may be balloon expandableand the branch portion self-expandable, or vice versa. Once the stent isin position in the main vessel and the branch portion is aligned withthe side branch the stent can be expanded. If the stent is balloonexpandable, the stent may be expanded with a single expansion ormultiple expansions. In particular, the stent can be deployed on a stentdelivery system having a balloon catheter and side sheath as described,for example, in U.S. Pat. Nos. 6,325,826 and 6,210,429, the entirecontents of which are incorporated herein by reference. In one preferredembodiment, a kissing balloon technique may be used, whereby one balloonis configured to expand the stent and the other balloon is configured toextend branch portion 30. After the main portion of the stent isexpanded in the main vessel, the stent delivery system may be removedand a second balloon may be passed through the side hole in the branchportion and expanded to expand the branch portion of the stent. In analternate embodiment, the same balloon may be inserted in the mainvessel inflated, deflated, retracted and inserted into the branchvessel, and then reinflated to expand branch portion 30 and cause it toprotrude into the branch vessel. Alternatively, the stent can bedelivered on two balloons and the main portion and the branch portioncan be expanded simultaneously. As needed, the branch portion can befurther expanded with another balloon or balloons. Yet anotheralternative is to use a specially shaped balloon that is capable ofexpanding the main and branch portions simultaneously. The stent canalso be deployed with other types of stent delivery systems.Alternatively, the stent, or portions of the stent, can be made of aself-expanding material, and expansion may be accomplished by usingself-expanding materials for the stent or at least branch portion 30thereof, such as Nitinol, Cobalt Chromium, or by using other memoryalloys as are well known in the prior art.

The construction and operation of catheters suitable for the purpose ofthe present invention are further described in U.S. patent applicationSer. No. 09/663,111, filed Sep. 15, 2000, which is acontinuation-in-part of U.S. patent application Ser. No. 09/614,472,filed Jul. 11, 2000, which is a continuation-in-part of U.S. patentapplication Ser. No. 09/325,996, filed Jun. 4, 1999, and Ser. No.09/455,299, filed Dec. 6, 1999, the disclosures of all of which areincorporated herein by reference. It should be noted that the catheterstaught in the above applications are exemplary, and that other cathetersthat are suitable with the stents of the subject application areincluded within the scope of the present application. In alternativeembodiments, catheters without balloons may be used. For example, if thestent is comprised of memory alloy such as Nitinol or Cobalt Chromium,or is a mechanically self-expanding stent, balloons are not necessarilyincluded on the catheters. Furthermore, any other catheter, includingones that are not disclosed herein, may be used to position stentsaccording to the present invention.

Referring now to FIGS. 25–28, illustrations of the steps of one exampleof a method for employing a stent according to the invention are shown.By way of example, the method is depicted utilizing stent 12. Methodsfor positioning such a catheter system within a vessel and positioningsuch a system at or near a bifurcation are described more fully inco-pending U.S. patent application Ser. No. 10/320,719 filed on Dec. 17,2002, which is incorporated herein by reference in its entirety. Asshown in FIG. 25, a catheter system 120 is positioned proximal to abifurcation, using any known method. A branch guidewire 122 is thenadvanced through an opening in the stent and into the branch vessel 4,as shown in FIG. 26. In a preferred embodiment, the opening may be adesignated side branch opening, such as an opening formed by the absenceof some connectors 26, as described above. Branch portion 30 is adjacentthe opening. As shown in FIG. 27, if the side sheath 124 is attached tothe main catheter 120, the main catheter 120 is advanced along with theside catheter 124. Alternatively, if the side sheath 124 is separatefrom to the main catheter 120, the second catheter or side sheath 124 isthen advanced independently through the opening in the stent and intothe branch vessel. Branch portion 30 is positioned over a portion of thelumen of the branch vessel 4 as the side sheath 124 is inserted intobranch vessel 4. Referring to FIG. 28, a first balloon 126 located onmain catheter 120 is then expanded, causing expansion of the stent body,and a second balloon 128 located on the second catheter or side sheath124 is also expanded, causing branch portion 30 to be pushed outwardwith respect to the stent body, thus providing stent coverage of atleast a portion of the branch vessel. The balloons are then deflated andthe catheter system and guidewires are then removed.

Referring now to FIGS. 29–31, illustrations of the steps of anothermethod for employing a stent of the present invention is shown. By wayof example, the method is depicted utilizing stent 12. The depictedmethod may be accomplished using a catheter system having a maincatheter 131 including a herniated balloon 135 (FIG. 32). In particular,the stent can be deployed on a stent delivery system having a herniatedballoon as described, for example, in U.S. Patent Application No.60/488,006, filed Jul. 18, 2003, the entire contents of which areincorporated herein by reference. As shown in FIG. 29, the catheter 131includes a balloon 135 that has a protruding portion 137 that protrudesoutwardly from the cylindrical outer surface 134 of the balloon.

Referring to FIG. 32, the herniated balloon 135, shown in an expandedstate, has a generally cylindrical shape and the protruding portion 137can be any appendage or integral portion of the balloon that movesoutwardly from the outer surface 134 of the balloon upon inflation, inaccordance with the principles of the invention. In a preferredembodiment, the protruding portion 137 is a portion of the balloon wallthat has greater expandability than other portions of the balloon wallthat retain a generally cylindrical shape. In another embodiment,protruding portion 137 may be a solid structure attached to the balloonwall. The protruding portion 137 can have any shape desirable to effectdeployment of branch portion 30. In one preferred embodiment, protrudingportion 137 has a hemispherical shape. In another preferred embodiment,protruding portion 137 has an ovoid shape. In use, the stent 12 iscrimped onto the balloon 135 so that the protruding portion 137 ispositioned at the branch portion. As shown, the protruding portion 137is positioned adjacent or alongside the radially inward side of branchportion 30. The herniated balloon 135 is used to expand the branchportion 30 and/or deploy the outwardly deployable structure of stent 12by applying a force in the laterally outward direction to the expandableelements by deflecting these elements toward the side branch 4. Theprotruding portion 137 may be located at any position along the lengthof the balloon. For example, it can be located on the middle ⅓ of thestent.

In one embodiment, the balloon may be constructed of compositematerials. For example, a combination of elastomeric and semi to noncompliant materials such as urethane, silicone, and latex, (Elastomeric)polyethylene hytrel pebax polyarylethertherketone, polyoxymethylene,polyamide, polyester thermoplastic polyetheretherketone andpolypropylene (semi to non compliant), may be used. The balloon may alsobe constructed by combining the above-mentioned materials with woventextiles such as Kevlar, silk cotton, wool, etc. In this construction, atextile is wound or woven onto a rod that has the shape of the desiredherniated balloon and the polymer is then extruded or dip coated overthe rod. The composite is cured, heat set or adhesively fused together.The rod is then removed and the remaining shape is a herniated balloon.The balloon can also be constructed by adding an appendage to aconventional balloon by using a molded collar or adhesively attaching anobject to the surface of the balloon or by using a mound of adhesive tocreate the herniation or protruding portion. In an alternate embodiment,the balloon can be constructed by molding three small balloons andattaching them in tandem with the center balloon being round in shape.The balloon would share a common inflation port. When the balloon isinflated the center balloon becomes the herniation.

Referring again to FIGS. 29–32, protruding portion 137 may be configuredto fit directly into an opening in the stent. As shown in FIG. 29,catheter 131 is advanced over a guidewire 133 and positioned proximal tothe bifurcation. As shown in FIG. 30, the catheter is advanced until theprotruding portion 137 of the balloon is positioned at the bifurcation.In one embodiment, protruding portion 137 protrudes outwardly fromcatheter 131 enough so that it actually comes into contact with thebifurcation, thus providing a method of alignment wit the branch vessel4. FIG. 31 shows that as the balloon 135 is expanded, it simultaneouslycauses the stent to expand and branch portion 30 to be pushed toward thebranch vessel 4. Upon inflation of the balloon, the herniated portion137 expands and extends through the branch portion 30 toward the sidebranch to open the entrance of the occluded side branch artery. FIG. 32shows a perspective view of the herniated balloon 135 extending along amain vessel axis 136.

In an alternative method, the stent can be delivered using a herniatedballoon and a dual lumen delivery system. This system can include a maincatheter defining a first lumen with concentric guidewire lumen andballoon inflation lumen, a herniated balloon, as described above, on themain catheter, a side sheath with a guidewire lumen, and a stent. Thestent is crimped over the main catheter, balloon and side sheath withthe side sheath exiting the stent through a branch opening or side hole.The distal end of the side sheath is used for aligning the stent branchopening with the branch vessel 4.

In another embodiment, the appendage or herniation may be located on asecond catheter or side sheath of the delivery system, such as thesystem 138 depicted in FIG. 33. In this case, the system is atwo-balloon system. The smaller balloon 140 can be positioned in thestent in a similar manner as the herniation. The appendage or herniationmay have an inflation lumen 141 and a lumen for receiving a guidewire142 for locating the branch vessel 4.

One particular application for the use of a stent with a branch portion30 such as the one described above is for localized drug delivery. Aswas discussed hereinabove, restenosis, including in-stent restenosis, isa common problem associated with medical procedures involving thevasculature. Pharmaceutical agents have been found to be helpful intreating and/or preventing restenosis, and these are best deliveredlocally to the site of potential or actual restenosis, rather thansystemically.

As used herein, the term “preventing” includes stopping or reducing theoccurrence or severity of a disease or condition or the symptoms of thedisease or condition.

As used herein, the term “treating” includes substantially reducing theseverity of a disease or condition or the symptoms of the disease orcondition, or substantially reducing the appearance of a disease orcondition or the symptoms of the disease or condition. The term“treating” includes substantially completely abolishing a disease orcondition or the symptoms of the disease or condition. The term“treating” also encompasses preventing, stopping, or reducing theoccurrence or severity of a disease or condition or the symptoms of thedisease or condition.

When—as with anti-restenosis drugs, for example—a drug is usefulprimarily at a particular body site, systemic administration is notnecessary and is often undesirable. For instance, systemicadministration of drugs often results in undesirable side effects. Also,it is difficult to achieve constant drug delivery to a site needingtreatment using systemic delivery methods. Drugs administeredsystemically often cycle through concentration peaks and valleys,resulting in time periods of toxicity and ineffectiveness. In contrast,drugs delivered in a localized manner can be delivered at a highconcentration at the site(s) where treatment is needed, while minimizingthe systemic concentration of the drug, thus minimizing or eliminatingside effects. Additionally, localized delivery facilitates themaintenance of appropriate drug levels at the treatment site, withminimal undesired fluctuation.

Stents according to the present invention may have one or more drugdepots on and/or in the stent wall. As used herein, the term “depot”describes a store of at least one drug designed to retain and thereafterrelease the drug(s). According to current technology, materialsincorporating drug(s) are often associated with stents by coating thedrug-containing material(s) onto the walls of the stents. Thus,“coating” is referred to and used herein in describing the depot(s), butthis use is solely for convenience of explanation and is in no waylimiting, and other methods of associating drug(s) with stents that arecurrently available or that may become available are specificallycontemplated. As another non-limiting example, as is discussed furtherhereinbelow, stents may be “seeded” with genetically engineered cellsthat secrete or otherwise release drug(s). As yet another non-limitingexample, biocompatible polymers incorporating drug(s) may be molded intoa solid mass of a desired size and shape and attached to the stent usingpharmaceutically acceptable methods.

The term “depot” refers generally to an area of a stent that is coatedor otherwise associated with drug(s) or a material incorporatingdrug(s). Any given depot is generally discrete from other depots. Forexample, in certain embodiments, a depot may consist of a discrete massof material incorporating drug(s). As another example, because the wallsof stents according to the present invention comprise open spaces, adepot may also include spaces. A depot may include open spaces, forexample, in embodiments where drug(s) or a material incorporatingdrug(s) is coated or seeded onto a stent to form the depot. One depotmay abut, or be adjacent to a second depot, but the second depot willgenerally have different drug(s) and/or different concentration(s) ofdrug(s), as is discussed in further depth hereinbelow.

It will be understood that depot(s) of stents according to the presentinvention can be “on” or “in” the stent walls. For example, where it isdesired to release drugs(s) primarily to the cells of the vessel wallsat the site of placement of a stent, it may be desirable to coat, attacha drug-containing mass, or otherwise associate drug(s) with only theouter side of the stent wall. As another example, when it is desired todeliver drug(s) to an organ, tissue, or region of the body downstreamfrom a stent, it may be desirable to coat, attach a drug-containingmass, or otherwise associate drug(s) with only the inner side of thestent wall. In still other embodiments, it may be desirable to coat,attach a drug-containing mass, or otherwise associate drug(s) with theinner side of the stent wall, the outer side of the stent wall, and/orthe portions of the stent wall that face inward to the open spaceswithin the wall.

The terms “drug,” “drug compound,” and “pharmaceutical agents” are usedinterchangeably herein, unless stated otherwise. These terms are meantto be construed broadly, to mean pharmaceutically acceptable substances(i.e., substances that are safe for use in the body of a mammal such asa human) and that have some biological effect on cells of the body. Theterms also include substances that are being tested for safety for usein the body of a mammal such as a human and/or to determine whether (orwhat) biological effect they have on cells of the body. Examples oftypes of molecules that may be drugs as the term is defined hereininclude, but are not limited to, proteins and peptides, small molecules,antibodies, multi-cyclical molecules, macrolides, and nucleic acids. Thegeneral and specific examples provided herein, as well as similarsubstances, are included in the term “drugs” according to the presentinvention.

Depots of stents according to the present invention are capablereleasing, or eluting, the stored drug(s). Hence, the depots of thepresent invention can be made of any material that can entrap,encapsulate, adhere, or otherwise retain and thereafter release thestored drug(s). Depots of stents according to the present invention arepreferably capable of controllably releasing drug(s). Hence, the depotsof the present invention are preferably made of any material that canentrap, encapsulate, adhere or otherwise retain and controllably releasethe stored drug(s).

The phrases “controllably release”, “controllable release,” and“controllably releasing” are used herein to describe a release ofdrug(s) at a predetermined rate and duration under selected conditions.Slow release is one form of controllable release.

In certain preferable embodiments, depots of the present inventioncomprise one or more biocompatible polymer(s) loaded with drug(s). Incertain embodiments, the biocompatible polymer utilized minimizesirritation to the wall of the lumen where the stent is implanted.Methods for incorporating biocompatible polymers loaded with drug(s)into or onto stents generally involve coating the stent with thepolymer(s) and are well known in the art. See, e.g., U.S. Pat. No.5,679,400.

Several configurations for loading drug(s) into biocompatible polymersare envisaged by the present invention. The drug(s) may be, for example,molded into the polymer, entrapped or encapsulated within the polymer,covalently attached to the polymer, physically adhered to the polymer,or otherwise incorporated into the biocompatible polymer.

The biocompatible polymer may be, for example, either a biostablepolymer or a biodegradable polymer, depending on factors such as thedesired rate of release or the desired degree of polymer stability underphysiological conditions.

Biodegradable polymers that are usable in the context of the presentinvention include, without limitation, poly(L-lactic add),polycaprolactone, poly(lactide-co-glycolide), poly(hydroxybutyrate),poly(hydroxybutyrate-co-valerate), polydioxanone, polyorthoester,polyanhydride, poly(glycolic acid), poly(D,L-lactic acid), poly(glycolicacid-co-trimethylene carbonate), polyphosphoester, polyphosphoesterurethane, poly(amino acids), cyanoacrylates, poly(trimethylenecarbonate), poly(iminocarbonate), copoly(ether-esters) (e.g. PEO/PLA),polyalkylene oxalates, polyphosphazenes and biomolecules such as fibrin,fibrinogen, cellulose, starch, collagen and hyaluronic acid.

Biostable polymers that are usable in the context of the presentinvention include, without limitation, polyurethanes, silicones,polyesters, polyolefins, polyisobutylene, ethylene-alphaolefincopolymers; acrylic polymers and copolymers, vinyl halide polymers andcopolymers, such as polyvinyl chloride; polyvinyl ethers, such aspolyvinyl methyl ether; polyvinylidene halides, such as polyvinylidenefluoride and polyvinylidene chloride; polyacrylonitrile, polyvinylketones; polyvinyl aromatics, such as polystyrene, polyvinyl esters,such as polyvinyl acetate; copolymers of vinyl monomers with each otherand olefins, such as ethylene-methyl methacrylate copolymers,acrylonitrile-styrene copolymers, ABS resins, and ethylene-vinyl acetatecopolymers; polyamides, such as Nylon 66 and polycaprolactam; alkydresins; polycarbonates; polyoxymethylenes; polyimides; polyethers; epoxyresins; polyurethanes; rayon; rayon-triacetate; cellulose, celluloseacetate, cellulose butyrate; cellulose acetate butyrate; cellophane;cellulose nitrate; cellulose propionate; cellulose ethers; andcarboxymethyl cellulose.

In certain other embodiments, depot(s) on or in stents according to thepresent invention comprise liposomes into which drug(s) have beenencapsulated or entrapped. Methods for incorporating liposomes loadedwith drug(s) into or onto stents generally involve coating the stentwith the polymer(s) and are known in the art. See, e.g., Kallinteri P.et al. “Dexamethasone incorporating liposomes: an in vitro study oftheir applicability as a slow releasing delivery system of dexamethasonefrom covered metallic stents,” Biomaterials 23(24): 4819–26 (2002). Inyet other embodiments, depot(s) depot(s) on or in stents according tothe present invention comprise genetically engineered cells that secreteor otherwise release desired drug(s), e.g., therapeutic protein(s).Methods for incorporating genetically engineered cells into or ontostents generally involve seeding the cells onto the stent and are knownin the art. See, e.g., Dichek, D. A. et al., “Seeding of IntravascularStents With Genetically Engineered Endothelial Cells”, Circulation, 80:1347–1353 (1989); Flugelman M. Y. et al., “Genetically engineeredendothelial cells remain adherent and viable after stent deployment andexposure to flow in vitro,” Circ Res., 70: 348–54 (1992).

One or more depots may be present at any location in or on the walls ofstents according to the present invention. Depot(s) may be utilized withany and all stents according to the present invention. Depot(s) may bepresent in or on the wall of the main vessel portion of stents accordingto the present invention. Similarly, depot(s) may be present in or onthe wall of the branch portion of stents according to the presentinvention. The position of depot(s) depends on desired site(s) ofhighest concentration of drug delivery.

The size of depot(s) on or in stents of the present invention depends onvarious parameters, such as the material of which the stent body isfabricated, the permeability of the stent body and the depot, theefficacy of the depot in retaining the drug(s), the concentration of thedrug(s), and the desired rate and duration of release of the drug(s).Depot(s) may extend around the entire, or only a portion of, thecircumference of main vessel portions of stents according to the presentinvention. Likewise, depot(s) may extend longitudinally for all or onlya portion of the length of main vessel portions of stents according tothe present invention. With regard to branch portions of stentsaccording to the present invention, depot(s) may cover all or only aportion of the walls, or may be in all or only a portion of the walls.

When it is desired to increase the overall volume of a depot, it mayoften be preferable to increase the length and/or width of the depot,rather than its thickness, or depth. In other words, it may often bepreferable to increase the size of a depot along or within the wall of astent, rather than extending the depot farther into the lumen of thestent. Depot(s) that extend too far into the lumen of a stent may impedefluid flow through the stent, and depots that are too thick on theoutside wall may deform the stent into the vessel, also impeding fluidflow. However, it may be desirable to concentrate a large volume ofdepot in a small surface area, to maximize drug concentration to a smallsection of vessel. Contrariwise, it may in other instances be desirableto have drug(s) released along a large section of vessel, in which casesit may be desirable to use a depot that has a large surface area alongor within a wall of the stent.

Thus, the length, width, and thickness of a depot are variables that canbe tailored according to the desired drug distribution and the size ofthe main and branch vessels to be treated. For example, a depot that isthick enough to impede fluid flow in a narrow vessel may be an optimalthickness for a larger vessel.

Additionally, the concentration of drug(s) in a depot can be variedaccording to the desired rate of elution of the drug from the depot andthe desired concentration of the drug in the local area of the depot.Thus, the parameters of depot length, width, and thickness and drugconcentration can be varied to tailor depots to elute the desiredconcentration of drug(s) to the desired area(s) in vessels of varyingsizes.

Non-limiting examples of anti-restenosis drugs that may be incorporatedinto depot(s) in or on stents according to the present invention includeanticoagulant agents, antiproliferative agents, antimigratory agents,antimetabolic agents, anti-inflammatory agents, and immunosuppressivesubstances, and combinations thereof. Particularly usefulanti-restenosis drugs include paclitaxel, rapamycin, and HDACinhibitors. Examples of histone deacetylase (HDAC) inhibitors, which areefficient inhibitors of smooth muscle cell (SMC) proliferation, include,without limitation, hydroxamic acids such as trichostatin A (TSA),suberoyl anilide hydroxamic acid (SAHA), oxamflatin, m-carboxycinnamicacid bishydroxamide (CBHA), cyclic hydroxamic acid-containing peptide 1(CHAP1), cyclic hydroxamic acid-containing peptide 31 (CHAP31), subericbishydroxamate (SBHA), pyroxamide, and scriptaid. Further detailspertaining to an HDAC inhibitors, their use, and stents incorporatingsame are disclosed in a U.S. Provisional Patent Application No.60/397,780 assigned to a common assignee of the present invention, filedJul. 24, 2002, entitled “STENTS CAPABLE OF CONTROLLABLY RELEASINGHISTONE DEACETYLASE INHIBITORS,” incorporated by reference herein in itsentirety.

In addition to anti-restenosis drugs, stents according to the presentinvention can also be used as vehicles for localized delivery of otherdrugs. As a non-limiting example, stents of the present invention areparticularly useful in for localized delivery of anti-thrombotic drugs.Thrombosis (the formation of a thrombus, or blot clot) sometimes occursin association with medical procedures involving the vasculature. Forexample, thrombosis may result from physical injury of an arterial wallby a vascular interventional procedure such as percutaneous transluminalcoronary angioplasty (“PTCA”; a type of balloon angioplasty) or coronarybypass surgery. Although thrombosis can result in death, the procedureswhich may have thrombosis as a side effect are themselves arelife-saving and widely used. Additionally, thrombosis may also resultfrom progression of a natural disease, such as atherosclerosis.Accordingly, administration of anti-thrombotic drugs to patients whohave undergone vascular procedures is often desirable.

Many anti-thrombotic drugs are known in the art. Non-limiting examplesinclude aspirin (acetylsalicylic acid), prostaglandin E₁, selectivethromboxane A₂ inhibitors, selective thrombin inhibitors, plateletreceptor GPIIb/IIIa blockers, tissue plasminogen activator,streptokinase, heparin, hirudin, bivalirudin, and kistrin and otherplatelet and/or thrombin inhibitors. As with anti-restenosis drugs,administration of anti-thrombotics locally to the site of potentialthrombosis is usually vastly preferable to systemic administration.

Additional, non-limiting examples of types of drugs that may beincorporated into depot(s) in or on stents according to the presentinvention include antineoplastic, antimitotic, antiplatelet, antifibrin,antithrombin, antibiotic, antioxidant, and antiallergic substances aswell as combinations thereof.

Depots for use in accordance with the present invention may include oneor more different drug(s). For example, it will often be desirable toinclude two or more drugs that have additive, or even synergisticeffects. Where more than one drug is incorporated into a single depot,it will be generally preferred to incorporate drugs that will notinterfere with, degrade, destabilize, or otherwise interfere with oneanother. However, in some cases in may be desirable to include a firstdrug along with a second drug that reduces or alters the activity of thefirst drug in a desired manner. In the same manner, different depots mayinclude different drugs, or different concentrations of the same drug.The many possible permutations allow for great flexibility in treatment.

Stents according to the present invention can be used as vehicles forlocalized delivery of drugs to cells of the walls of both the main andbranch vessels at the location of the stent. Drugs that are particularlysuitable for treatment of cells in the immediate area of the stentinclude anti-restenosis and anti-thrombotic drugs. If desired, differentconcentrations of drugs, or different drugs, may be included in depot(s)located in or on different areas of the stent walls. For example, it maybe desirable to treat the cells of the main vessel with a first drug,combination of drugs, and/or concentration of drug(s) and to treat thecells of the branch vessel with a second, different, drug, combinationof drugs, and/or concentration of drug(s). As another example, it may bedesirable to maintain a high concentration of anti-restenosis drug(s)near the bifurcation of the vessels. As yet another non-limitingexample, it may be desirable to maintain a high concentration ofanti-restenosis drug(s) at the three open ends (two on the main portionand one on the branch portion) of the stent. It will be appreciated byone skilled in the art upon reading the present disclosure that manycombinations of two or more depots are possible within the spirit andscope of the present invention.

Stents according to the present invention can be used as vehicles todeliver drug(s) to an organ, tissue, or region of the body downstreamfrom the stent. For example, stents according to the present inventionmay be positioned in an artery that supplies blood to an organ, such asthe heart, in a location close to that organ. Drug(s) that elute fromthe depot(s) in or on the stent may be carried by the blood flow to theorgan. In this way, localized delivery to tissues, organs, and bodyregions can be achieved. Using stents according to the presentinvention, a first drug, combination of drugs, and/or concentration ofdrug(s), may be delivered to an organ, tissue, or region downstream fromthe main portion of the stent while a second, different, drug,combination of drugs, and/or concentration of drug(s) is delivered to anorgan, tissue, or region downstream from the branch portion of thestent. This differential delivery can be accomplished by locating adepot having a first drug, combination of drugs, and/or concentration ofdrug(s) in or on an area of the main portion of the stent that is notcontacted by blood flowing through the branch vessel, and locating asecond depot having a second, different, drug, combination of drugs,and/or concentration of drug(s) in or on the branch portion of thestent. It will be appreciated by one skilled in the art upon reading thepresent disclosure that many combinations of two or more depots arepossible within the spirit and scope of the present invention.

Specific, and non-limiting, examples of drugs that may be incorporatedinto depot(s) in or on stents according to the present invention includethe following drugs. Examples of antineoplastic and/or antimitotic drugsinclude docetaxel (e.g., Taxotere® from Aventis S. A., Frankfurt,Germany) methotrexate, azathioprine, vincristine, vinblastine,fluorouracil, doxorubicin hydrochloride (e.g., Adriamycin® fromPharmacia & Upjohn, Peapack N.J.), and mitomycin (e.g., Mutamycin® fromBristol-Myers Squibb Co., Stamford, Conn.). Examples of antiplatelet,anticoagulant, antifibrin, and antithrombin drugs include sodiumheparin, low molecular weight heparins, heparinoids, hirudin,argatroban, forskolin, vapiprost, prostacyclin and prostacyclinanalogues, dextran, D-phe-pro-arg-chloromethylketone (syntheticantithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membranereceptor antagonist antibody, recombinant hirudin, and thrombininhibitors such as Angiomax™ (Biogen, Inc., Cambridge, Mass.). Examplesof cytostatic or antiproliferative drugs include angiopeptin,angiotensin converting enzyme inhibitors such as captopril (e.g.,Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.),cilazapril or lisinopril (e.g., Prinivil® and Prinzide® from Merck &Co., Inc., Whitehouse Station, N.J.); calcium channel blockers (such asnifedipine), colchicine, fibroblast growth factor (FGF) antagonists,histamine antagonists, lovastatin (an HMG-CoA reductase inhibitor, brandname Mevacor® from Merck & Co., Inc., Whitehouse Station, N.J.),monoclonal antibodies (such as those specific for Platelet-DerivedGrowth Factor (PDGF) receptors), nitroprusside, phosphodiesteraseinhibitors, prostaglandin inhibitors, suramin, serotonin blockers,steroids, thioprotease inhibitors, triazolopyrimidine (a PDGFantagonist), and nitric oxide. An example of an antiallergic agent ispermirolast potassium. Other therapeutic substances or agents that maybe used include alpha-interferon and dexamethasone. The preventative andtreatment properties of the foregoing therapeutic substances or agentsare well-known to those of ordinary skill in the art.

The present invention also provides kits comprising a stent or stentsaccording to the present invention. In addition to a stent or stents, akit according to the present invention may include, for example,delivery catheter(s), balloon(s), and/or instructions for use. In kitsaccording to the present invention, the stent(s) may be mounted in or ona balloon or catheter. Alternatively, the stent(s) may be separate fromthe balloon or catheter and may be mounted therein or thereon prior touse.

A stent for use in a bifurcated body lumen having a main branch and aside branch. The stent comprises a radially expandable generally tubularstent body having proximal and distal opposing ends with a body wallhaving a surface extending therebetween. The surface has a geometricalconfiguration defining a first pattern, and the first pattern has firstpattern struts and connectors arranged in a predetermined configuration.The stent also comprises a branch portion comprised of a second pattern,wherein the branch portion is at least partially detachable from thestent body.

1. A stent for implantation in a bifurcated body lumen having a mainbranch and a side branch, wherein the stent comprises: a tubular bodyhaving an opening with a proximal side and a distal side and a distalend and a proximal end, the tubular body comprises a first pattern ofrows of struts and connectors, the rows of struts are connected to eachother by said connectors; a branch portion positioned adjacent to theopening between said distal end and said proximal end of said tubularbody, wherein in a first configuration said branch portion is flush withsaid tubular body and in a second configuration said branch portion isextended outward with respect to the tubular body and in which thebranch portion extends away from both the proximal side and the distalside of the opening.
 2. The stent of claim 1, wherein said branchportion comprises a second pattern of rows of struts and connectors,wherein said second pattern of rows of struts and connectors has adifferent configuration than said first pattern of rows of struts andconnectors.
 3. The stent of claim 2, wherein said differentconfiguration includes different strut lengths.
 4. The stent of claim 2,wherein said different configuration includes at least one row having adifferent strut density.
 5. The stent of claim 1 in which: the branchportion further comprises a first ring connected by a first ringconnector to the tubular body and a second ring connected by second ringconnector to the first ring, when in the first configuration the firstring is concentric with the second ring, and when in the firstconfiguration the first and second rings define ring patterns each ofwhich is a complete circuit extending from a first side of the first orsecond ring connector respectively to the second side of the samerespective ring connector, when in the first configuration the first andsecond rings are flush with the tubular body and when in the secondconfiguration the first and second rings extend outwardly from thetubular body.
 6. The stent according to claim 5, wherein the tubularbody has a longitudinal axis and the branch portion is disposedsubstantially perpendicular to the longitudinal axis in the secondconfiguration.
 7. The stent according to claim 5, wherein the branchportion includes a support ring.
 8. The stent according to claim 7,wherein the support ring is a continuous loop.